title: Hantaviral mechanisms driving HLA class I antigen presentation require both RIG-I and TRIF.
abstract: Hantaviruses are emerging human pathogens. They induce an unusually strong antiviral response of human HLA class I (HLA-I) restricted CD8⁺ T cells that may contribute to tissue damage and hantavirus-associated disease. In this study, we analyzed possible hantaviral mechanisms that enhance the HLA-I antigen presentation machinery. Upon hantavirus infection of various human and primate cell lines, we observed transactivation of promoters controlling classical HLA molecules. Hantavirus-induced HLA-I upregulation required proteasomal activity and was associated with increased TAP expression. Intriguingly, human DCs acquired the capacity to cross-present antigen upon hantavirus infection. Furthermore, knockdown of TIR domain containing adaptor inducing IFN-β or retinoic acid inducible gene I abolished hantavirus-driven HLA-I induction. In contrast, MyD88-dependent viral sensors were not involved in HLA-I induction. Our results show that hantaviruses strongly boost the HLA-I antigen presentation machinery by mechanisms that are dependent on both retinoic acid inducible gene I and TIR domain containing adaptor inducing IFN-β.
authors.affiliation: Institute of Medical Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Pritesh
authors.initials: P
authors.lastname: Lalwani
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Raftery
authors.forename: Lidija
authors.initials: L
authors.lastname: Kobak
authors.forename: Andreas
authors.initials: A
authors.lastname: Rang
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Markus
authors.initials: M
authors.lastname: Matthaei
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van den Elsen
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wolff
authors.forename: Detlev H
authors.initials: DH
authors.lastname: Krüger
authors.forename: Günther
authors.initials: G
authors.lastname: Schönrich
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation; D002522:Chlorocebus aethiops; D045142:Cross-Priming / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D006476:Orthohantavirus / Q000276:immunology*; D018778:Hantavirus Infections / Q000276:immunology*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014709:Vero Cells
chemical_list: D018528:ATP-Binding Cassette Transporters; D033942:Adaptor Proteins, Vesicular Transport; D006680:HLA Antigens; C437968:PLAAT4 protein, human; D034741:RNA, Small Interfering; D018168:Receptors, Retinoic Acid; C470409:TICAM1 protein, human; D046988:Proteasome Endopeptidase Complex
keywords: Antigen presentation/processing; Cross-presentation/priming; Immunopathology; Infectious diseases; Innate immunity